The Effect of Vitamin D on Expression of TGF β1 in Ovary

N. Corduk; G. Abban; B. Yildirim; A. Sarioglu-Buke

doi:10.1055/s-0032-1314858

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2012; 120(08): 494-493
DOI: 10.1055/s-0032-1314858

Article

The Effect of Vitamin D on Expression of TGF β1 in Ovary

N. Corduk

¹Pediatric Surgery, Pamukkale University School of Medicine, Denizli, Turkey

,

G. Abban

²Histology and Embryology, Pamukkale University, Denizli, Turkey

,

B. Yildirim

³Obstetrics and Gynecology, Pamukkale University School of Medicine, Denizli, Turkey

,

A. Sarioglu-Buke

¹Pediatric Surgery, Pamukkale University School of Medicine, Denizli, Turkey

› Author Affiliations

Abstract

The transforming growth factor β (TGF-β) is thought to have important roles in several stages of folliculogenesis. Vitamin D is effective in cell proliferation, differentition and on estrogen biosynthesis. The aim of the present study was to determine the respective role of 1,25-dihydroxyvitamin D3 on expression of TGF-β1 in developing rat ovaries. 24 (one-mounth-old n=12 and adult n=12) female Wistar rats were enrolled in this study. All animals were divided into 4 groups. Group I and II that consist of one-month-old (n=6) and adult rats (n=6) respectively served as control groups. Intramuscular vitamin D3 ( 0,05 μgr/kg/every other day) was injected for 8 weeks to group III and IV which consist of one-mounth-old and adult rats respectively. After last injection, ovaries of animals were removed and processed for immunohistochemistry assay. No remarkable differences in staining intensity and localization for TGF-β1 were observed in group I and group III. TGF immunostaining was also predominantly found in oocytes. In granulosa cells, TGF-β1 immunoreactivity was negative. TGF-β1 immunostaining were observed both in nuclei and cytoplasm of granulosa cells in group II. But in group IV granulosa cells and oocytes were negative for TGF-β1. We found that vitamin D administration resulted in a decrease in TGF-β1 levels in the adult rats, but, TGF-β1 expression did not significantly decrease in the newborn rats. However, in multiple linear regression analysis, TGF-β1 expressions were independently associated with vitamin D administration. It is observed that Vitamin D attenuated TGF-β1 expression. The results of this study suggest that vitamin D may play role in folliculogenesis via TGF-β1.

Key words

ovary - Vitamin D - TGF-β1

Full Text

References

References
1 Akhurst RJ. TGF beta signaling in health and disease. Nat Genet 2004; 36: 790-792
2 Barkhem T, Nilsson S, Gustafsson JA. Molecular mechanisms, physiological consequences and pharmacological implications of estrogen receptor action. Am J Pharmacogenomics 2004; 4: 19-28
3 Chen YG, Wang XF. A special issue on TGF-beta signaling. Cell Res 2009; 19: 1-2
4 Couse JF, Korach KS. Estrogen receptor null mice: what have we learned and where will they lead us?. Endocr Rev 1999; 20: 358-417
5 Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. Reproduction 2001; 122: 829-838
6 Halloran BP, DeLuca HF. Effect of vitamin D deficiency on fertility and reproductive capacity in the female rat. J Nutr 1980; 110: 1573-1580
7 Hayashi M, McGee EA, Min G et al. Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles. Endocrinology 1999; 140: 1236-1244
8 Ito I, Hanyu A, Wayama M et al. Estrogen inhibits transforming growth factor beta signaling by promoting Smad2/3 degradation. J Biol Chem 2010; 285: 14747-14755
9 Juengel JL, McNatty KP. The role of proteins of the transforming growth factor-beta superfamily in the intraovarian regulation of follicular development. Hum Reprod Update 2005; 11: 143-160
10 Knight PG, Glister C. TGF-beta superfamily members and ovarian follicle development. Reproduction 2006; 132: 191-206
11 Kinuta K, Tanaka H, Moriwake T et al. Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology 2000; 141: 1317-1324
12 Massagué J. TGF-beta signal transduction. Annu Rev Biochem 1998; 67: 753-791
13 Massagué J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol 2000; 1: 169-178
14 Massagué J, Wotton D. Transcriptional control by the TGF-beta/Smad signaling system. EMBO J 2000; 19: 1745-1754
15 McGee EA, Smith R, Spears N et al. Mullerian inhibitory substance induces growth of rat preantral ovarian follicles. Biol Reprod 2001; 64: 293-298
16 Shi Y, Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003; 113: 685-700
17 Studzinski GP, McLane JA, Uskokovic MR. Signaling pathways for vitamin D-induced differentiation: implications for therapy of proliferative and neoplastic diseases. Crit Rev Eukaryot Gene Expr 1993; 3: 279-312
18 Stumpf WE. Vitamin D sites and mechanisms of action: a histochemical perspective. Reflections on the utility of autoradiography and cytopharmacology for drug targeting. Histochem Cell Biol 1995; 104: 417-427
19 Thomas FH, Armstrong DG, Tefler EE. Activin promotes oocyte development in ovine preantral follicles in vitro. Reprod Biol Endocrinol 2003; 1: 76-83
20 Thomas FH, Ethier JF, Shimasaki S et al. Follicle-stimulating hormone regulates oocyte growth by modulation of expression of oocyte and granulosa cell factors. Endocrinology 2005; 146: 941-949
21 Walters MR. Newly identified actions of the vitamin D endocrine system. Endocr Rev 1992; 13: 719-764
22 Wrana JL. Crossing Smads. Sci STKE 2000; 2000 re1
23 Yoshizawa T, Handa Y, Uematsu Y et al. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet 1997; 16: 391-396